Treatment admissions for cannabis-related problems have more than doubled since the mid 1990's. Clinical trials indicate that a majority of those who enter treatment for cannabis problems relapse, and relapse rates are comparable to those observed for other drugs of abuse. Currently there are no accepted pharmacotherapies for treating cannabis dependence. Dronabinol (Marinol(r)) has exhibited effects in prior studies suggesting potential for treating cannabis dependence, but these studies involved dronabinol administration 3-5 times per day, which raises some concerns with regards to potential impairment of cognitive and psychomotor abilities, medication adherance, and potential for diversion. The present proposal will extend previous research on medications development for the treatment of cannabis use disorders by examining the effects of zolpidem extended-release (Ambien CR(r)) administered at bedtime on cannabis withdrawal severity, objective sleep measures, and presence of side-effects. This medication was selected for study because it has been demonstrated to reverse sleep problems, a prominent symptom of cannabis withdrawal, and sleep research suggests that it is possible that amelioration of sleep dysfunction may result in an attenuation of other cannabis withdrawal effects such as anxiety, depression, and anger. This line of research is also attractive because zolpidem and several other sleep medications are purported to have fewer side effects and less abuse liability compared with dronabinol, however, these effects have not been assessed in controlled studies of cannabis users. The proposed experiment will carefully study the effects of zolpidem (12.5mg) and placebo in daily cannabis users during brief periods of abrupt cannabis abstinence. Using a within-subjects crossover design, participants will sequentially complete periods of baseline ad-libitum cannabis smoking, abrupt cannabis abstinence with medication, and a return to baseline prior to the next abstinence period. Cannabis withdrawal severity, sleep polysomnography (PSG), performance on a comprehensive battery of state-of-the-art cognitive and psychomotor tests, and subjective ratings of medication side effects will be assessed daily in each phase of the study. Outcomes from this experiment will provide initial information regarding whether medications known to improve sleep function are safe and effective alternatives to dronabinol for use as pharmacotherapies in the treatment of cannabis dependence, and will provide new data regarding the effects of chronic cannabis use and withdrawal on sleep architecture. PUBLIC HEALTH RELEVEANCE: The number of people seeking treatment for marijuana-related problems is on the rise, yet there is no currently accepted medication proven to help them quit. This research is designed to investigate the ability of the FDA approved sleep medication zolpidem extended-release (Ambien CR(r)) to reduce the withdrawal effects associated with stopping daily marijuana use, and to carefully study the effects of quitting marijuana on sleep functioning and the occurance of safety risks and side-effects associated with the medication in marijuana users.